How To Write A Cervical Cancer Screening Guidelines

Transcription

1 Cervical Cancer Screening Recommendations, 2012 Herschel W. Lawson, MD, FACOG Chief Medical Officer, ASCCP Adjunct Associate Professor, Gyn-OB, Emory University School of Medicine, Atlanta, GA.

2 Disclosures Chief Medical Officer, ASCCP (paid) Editor in Chief, Journal of Lower Genital Tract Disease (paid) Adjunct Associate Professor, Emory University School of Medicine, Department of Gynecology and Obstetrics (volunteer) Industry No relationship

3 Today s Presentation Objectives Describe 2012 ACS/ASCCP/ASCP cervical cancer screening guidelines Compare the new guidelines to the 2012 USPSTF screening guidelines Introduce use of an FDA approved HPV test (2014) for primary cervical cancer screening

4 Objectives of Screening Prevent morbidity and mortality from cervical cancer Prevent overzealous management of Prevent overzealous management of precursor lesions that most likely will regress or disappear and for which the risks of management outweigh the benefits

5 Courtesy of Hallmark Shoebox Greetings, Hallmark, Inc. Hallmark Cards, Inc.

6 Natural History of Cervical Cancer HPV infection CIN 1 Avg mo CIN 2,3 Avg yrs Invasive CA Avg mo. HPV disappearance

7 Being rarely or never screened is the major contributing factor to most cervical cancer deaths today.

8 Who are the Rarely and Never Screened? Descriptions Minorities Low SES* Foreign born Living in the US < 10 years No usual source of health care Where are the data? US Census NCHS Cervical cancer mortality BRFSS µ NHIS** * Socio-economic status National Center for Health Statistics, CDC µ Behavioral Risk Factor Surveillance System, CDC ** National Health Interview Survey, CDC

9 System Failures Leading to Cervical Cancer Diagnosis Patient does not get appropriate therapy Health care providers do not screen women at visits Patient gets cervical cancer Colposcopy for abnormal screen not done Women do not come in for screening Courtesy of Connie Trimble, MD, Johns Hopkins University School of Medicine, Baltimore, MD

10 Retrospective Study of Cervical Cancers Diagnosed at Kaiser Northern California Cytology results 3-36 months prior to diagnosis Failure to screen No cytology 464 (56%) N=833 Failure in detection 1 st cytol.norm. 263 (32%) Failure to follow-up 1 st cytology abnormal 106 (13%) 464 (56%) 263 (32%) abnormal No visit 19% 1-2 visits 18% >3 visits 63% Leyden MA, Manos M, Kinney W et al JNCI 2005;97:

11 Why isn t finding lesions the objective of screening? Don t know which lesions will progress. Need to place emphasis on: Persistent HPV infections CIN3 (no margin for error) CIN2 in older women (no risk to pregnancies) Persistent CIN2 and CIN2/3 in nonadolescent women

12 Consensus Conference Sponsored by American Cancer Society (ACS) American Society for Colposcopy and Cervical Pathology (ASCCP) American Society for Clinical Pathology (ASCP)

13 ACS/ASCCP/ASCP Guidelines Development Process A steering committee from the 3 organizations created 6 working groups and a data group to direct the evidence evaluation Participating organizations: AHRQ, AAFP, ABOG, ACHA, ACOG, ASHA, ASC, ASCT, CAP, CDC, CMS, FDA, NCI, NCCN, NPWH, PPFA, SCC, SGO, SGOC, USPSTF, VHA

14 Guidelines Development Evidence Review Used Grading Recommendations Assessment, Development, and Evaluation (GRADE) system (grade.org) Articles retrieved 1995 to mid-2011 WGs reviewed and graded evidence as critical, important, and nice to know WGs developed recommendations -- strong or weak depending on the quality of the evidence

15 ACS/ASCCP/ASCP Guidelines Development Process 6 topic areas identified: Optimal screening intervals Screening women 30+ Managing discordant cytology/hpv results Exiting women from screening Impact of HPV vaccination on screening Potential for primary HPV testing (no cytology)

16 Guidelines Development Process Principles & Assumptions Preventing all cervical cancer is unrealistic A reasonable risk strategy should be cytology alone at 2-3y intervals Screening strategies with similar outcomes are acceptable Women at similar risk for cancer should be managed the same

17 Guidelines Development Process Principles & Assumptions (2) Conventional and liquid-based cytology perform similarly Screening interval Risk of developing invasive cancer before next screen should be unlikely Earlier detection of CIN3+ is a benefit Even studies with less sensitive tests show similar CIN3 detection--no increased cancer risk during later screening rounds

18 Guidelines Development Process Principles & Assumptions (3) Possible harms of screening Anxiety over a positive test Stigma of an STI Pain/bleeding from procedures Treatment-related pregnancy complications Number of colposcopies performed is a marker for harms

19 Treatment saves lives, but at what cost? Risk of unanticipated reproductive outcomes Risk rises with depth and number of LEEPs 2014 report suggests all women with CIN2+ have risk whether treated or not Kyrgiou M et al. Lancet 2006;367: Bruinsma et al BJOG 2007;114:70-80

20 Guidelines Development Evidence Review Process Recommendations posted to ASCCP website for public comment 10/19-11/9/11 Revisions made based on comments as needed Consensus conference held 11/17-18/2011 Discussion of draft recommendations by attendees Recommendations approved by at least a 2/3 majority of delegates

21 2012 ACS/ASCCP/ASCP Cervical Cancer Screening Guidelines* Guidelines do not apply to special populations hx of cervical cancer, DES exposure, & immune-compromise Saslow D, Solomon D, Lawson H, et al. CA: A Cancer J for Clinicians. 2012;62(3):147-72

22 New ACS/ASCCP/ASCP Guidelines When to begin screening Cervical cancer screening should begin at age 21. Women < 21 should not be screened regardless of age of sexual onset Saslow D, Solomon D, Lawson H, et al. CA: A Cancer J for Clinicians. 2012;62(3):147-72

23 Trends in Cervical Cancer Among Women < Age 40, SEER, United States, , by 5 Year Age Groups Benard VB, Watson M, Castle PE, Saraiya M. Cervical carcinoma rates among young females in the United States. Obstet Gynecol. Nov 2012;120(5):

24 Cervical Cancer Incidence and Mortality Rates per 100,000 women, United States, Age Incidence US Death Average annual count of 21 cases of invasive cervical cancer in year olds. Benard VB, Watson M, Castle PE, Saraiya M. Cervical carcinoma rates among young females in the United States. Obstet Gynecol. Nov 2012;120(5):

25 Histopathology Dx For Women Ages < 40 Carcinomas (n = 24,248) 70% Squamous cell 25% Glandular (adeno- and adeno-squamous) 5% Other Non-carcinomas (n = 310) 30% were childhood sarcomas 100% diagnosed in 0-14 year olds 80% diagnosed in year olds Benard VB, Watson M, Castle PE, Saraiya M. Cervical carcinoma rates among young females in the United States. Obstet Gynecol. Nov 2012;120(5):

26 Adolescent Needs HPV, Tdap and Meningococcal vaccines, Care for contraception STI screening/treatment STI testing can be done using urine No cervical cancer screening No speculum exam for asymptomatic women

27 Screening for ages 21-29* Cytology alone every 3 years HPV testing should not be used to screen Not as a component of cotesting Not as a primary stand-alone screen *2012 ACS/ASCCP/ASCP screening guidelines; prior to FDA approval of cobas HPV for primary screening.

28 Rationale for Longer Cytology Screening Intervals Sensitivity of single Pap test 50-70% Cancer risk 18mo after 3 neg Paps = 1.5/100,000 Cancer risk 36mo after 3 neg Paps = 4.7/100,000 99,997 women screened unnecessarily to help 3 Risk of HSIL/cancer <3 years after negative Pap not significantly higher than risk after 1year Longer Pap screening intervals (e.g., 5y) inappropriate for mobile US population Sawaya GF et al. Acta Cytol 2005;49:391-7

29 Rationale for Longer Cytology Screening Intervals-2 Screening harms: lifetime risk of colposcopy Screening q3y: 760 colpos/1000 women Screening q2y: 1080 colpos/1000 women Screening annually: 2000 colpos/1000 women Stout NK et al. Arch Intern Med 2008;168:181. Kulasingam S et al AHRQ Publication No EF-1.

30 Weighted Prevalence of Low-risk and High-risk HPV Types Among US Women 14 59yo, (NHANES) Hariri S et al. J Infect Dis. 2011;204:

31 Rationale for Avoiding HPV Tests Among Women Ages Prevalence of carcinogenic HPV approaches 20% in teens and early 20s Most carcinogenic HPV infections resolve without intervention Identifying carcinogenic HPV that will resolve leads to repeated call-back, anxiety, and interventions without benefit

32 Screening For Women Ages Cytology + HPV testing (cotesting) every 5 years is preferred Cytology alone every 3 years is acceptable

33 Rationale for Cotesting, Ages Increased detection of prevalent CIN3 Decreased CIN3 in subsequent screening rounds Achieves risk of CIN3 equal to cytology 1-3year intervals Enhances detection of adenocarcinoma/ais Minimizes the increased number of colposcopies, thus reducing harms.

34 Why Not Annual Cotesting? High NPV of one cotest means most abnormal screens at 1-3y intervals are transient HPV infection, not precancer Potential harms are amplified without benefit

35 Rapid clearance of HPV in Women >30 8% * 61% * Histological progression Rodriguez AC et al. J Natl Cancer Inst. 2008;100:

36 Managing HPV+/Cytology- Cotests Women cotesting HPV positive and cytology negative should be followed with either: 1) Repeat cotesting in 12 months, or 2) Immediate HPV genotyping for HPV16 alone or HPV 16/18. Direct referral to colposcopy is not indicated

37 1) Repeat cotest in 12 months If either repeat test is positive, refer to colposcopy If both tests are negative, return to routine If both tests are negative, return to routine screening.

38 2) Immediate HPV genotyping If HPV 16 or HPV16/18 positive, refer directly to colposcopy. If HPV 16 or HPV 16/18 negative, repeat cotest in 12 months and then If either repeat test is positive, refer to colposcopy If both tests are negative, return to routine screening.

39 Managing HPV+/Cytology- Cotests Rationale Consistent observational data indicate short term risk of CIN3 far below risk threshold of HPV+/ASC-US and LSIL used for colposcopy referral Evidence from cohort studies shows majority of transient infections clear by 12 months allowing most to return to routine screening without excessive risk.

40 When to Stop Screening age 65 if adequate negative prior screening. No CIN2+ within the last 20 years. Definition of adequate negative screening: 3 consecutive negative cytologies or 2 consecutive negative HPV tests (Tests within 10 years of stopping; most recent within 5 years.)

41 Stop screening at age 65 Screening should not resume for any reason, even if a woman reports having a new sexual partner.

42 Rationale For Stopping at Age 65 CIN2+ is rare after age 65 Most abnormal screens, even HPV+, are false + and do not reflect precancer HPV risk remains 5-10% Colposcopy/biopsy/treatment more difficult Harms are magnified Incident HPV infection unlikely to lead to cancer within remaining lifetime Chen HC et al. JNCI 2011;103: ; Rodrigues AC et al. JNCI 2009;101:721-8

43 When to stop screening - 2 Stop after hysterectomy with removal of cervix and no history of CIN2+. Evidence of adequate negative prior screening is not required.

44 Stopping Screening after Hysterectomy: Rationale Vaginal cancer rate = 7/million/year 663 vag. cuff cytologies needed per 1 VAIN 2,066 women followed after hysterectomy for average 89 months 3% had VAIN, 0 had cancer Risk of cytology abnormality after hyst = 1%. Compare to risk of breast cancer in men for which screening is not recommended. Pearce KF et al. NEJM 1996;335: ; Piscitelli JT et al. AJOG 1995;173:424-30

45 When NOT to stop at age 65 If cotest result is ASC-US/HPV- * If history of CIN2, CIN3, or AIS (CIN2+) Continue routine screening for at least 20 years, even if this extends screening past age 65. *2013 ASCCP Management Guidelines

46 Screening a Vaccinated Cohort Recommended screening practices should not change on the basis of HPV vaccination. Vaccination against HPV 16/18 Reduces CIN3+ by 17-33% Reduces colposcopy by 10% Reduces treatment by 25% But who is vaccinated? Recall? Completed series? HPV naïve? Paavonen J et al. Lancet 2009;374:301-14

47 HPV as a Primary Screening Test* Strong NPV of HPV test suggests it might replace cotesting, but test specificity lacking Follow-up to HPV+ test remains unclear Pap? Repeat HPV in 1y? Genotyping? Colpo? Knowing HPV status biases cytology reports to abnormal Harms undefined No US prospective trials published to date In most clinical settings, women ages should not be screened with HPV testing alone. *2012 ACS/ASCCP/ASCP Consensus conference for cervical cancer screening.

48 Comparison of ACS/ASCCP/ASCP, ACOG and USPSTF Guidelines, 2012 ACS,ACOG,2012 USPSTF,2012 Age to start Age 21 Age 21 Women Cytology every 3 years Cytology every 3 years Women Women >65 Post- Hysterectomy Cotesting every 5 years (preferred) or Every 3 years with Pap alone Discontinue after age 65 years with adequate negative screening Discontinue if for benign reason Cotesting every 5 years or Every 3 years with Pap alone Discontinue after age65 years with adequate negative screening Discontinue if for benign reason Saslow D, Solomon D, Lawson H, et al. CA: A Cancer J for Clinicians. 2012;62(3): ACOG. ACOG Practice Bulletin Number 131: Screening for cervical cancer. Obstet Gynecol. Nov 2012;120(5): Moyer VA. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Annals of internal medicine. Jun ;156(12):

49 HPV Primary Screening for Cervical Cancer FDA approval of cobas HPV test, April, 2014 Athena end of trial results pending. >40,000 participants age 25 Followed up in 3 years if HPV test negative Colposcopy if HPV 16+ or 18+ Cytology if HPV 16 neg. or 18 neg. Interim recommendations developed by ASCCP/SGO to be published soon Downstream management currently uncertain as few long term data exist.

50 HPV as the Initial Screening Test Screen with hrhpv (>25 years) hrhpv (-) hrhpv (+) Triage Test Performed (cytology / genotyping / p16) Rescreen in 3 yrs (-) (+) Rescreen at some interval Colpo

51 Current Screening Dilemma Can we integrate the 2 screening systems? At what age should cotesting or 1 o HPV screening begin? What is a reasonable screening interval for a negative HPV test? What about screening intervals if vaccine uptake is sufficient? Is there additional benefit to cotesting vs. 1 o HPV testing alone? Will other approved HPV products be available soon? Will the community revolt and regress to 3 year screening?

52 Conclusions The biggest gain in reducing cervical cancer incidence and mortality would be achieved by increasing screening rates among women rarely or never screened... Clinicians, hospitals, health plans, and public health officials should seek to identify and screen these women. ACA Health Plans expected to cover cytology and HPV testing without copayment per screening recommendations. ACS, 2002, 2012

53 Caveats Clinicians, patients, third-party payers, institutional review committees, other stakeholders, or the courts should never view recommendations as dictates. Even strong recommendations based on high-quality evidence will not apply to all circumstances and all patients. Users of guidelines may reasonably conclude that following some strong recommendations based on high quality evidence will be a mistake for some patients. No clinical practice guideline or recommendation can take into account all of the often compelling unique features of individual patients and clinical circumstances. Thus, nobody charged with evaluating clinician s actions, should attempt to apply recommendations in rote or blanket fashion.